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基于捕获拟南芥脂质代谢自然变异性模型的基因功能鉴定。

Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism.

机构信息

Bioinformatics, Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.

Systems Biology and Mathematical Modelling, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.

出版信息

Nat Commun. 2023 Aug 14;14(1):4897. doi: 10.1038/s41467-023-40644-9.

DOI:10.1038/s41467-023-40644-9
PMID:37580345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10425450/
Abstract

Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation. Here, we present the Plant Lipid Module (PLM) which provides a mechanistic description of lipid metabolism in the Arabidopsis thaliana rosette. We demonstrate that the PLM can be readily integrated in models of A. thaliana Col-0 metabolism, yielding accurate predictions (83%) of single lethal knock-outs and 75% concordance between measured transcript and predicted flux changes under extended darkness. Genome-wide associations with fluxes obtained by integrating the PLM in diel condition- and accession-specific models identify up to 65 candidate genes modulating A. thaliana lipid metabolism. Using mutant lines, we validate up to 40% of the candidates, paving the way for identification of metabolic gene function based on models capturing natural variability in metabolism.

摘要

脂质在调节农艺重要性状方面发挥着基本作用。植物脂质代谢的进展直到最近才在很大程度上基于还原论方法,尽管其成分的调节可能会产生全系统的影响。然而,现有的植物脂质代谢模型提供了综合的表示,阻碍了对成分调节的详细研究。在这里,我们提出了植物脂质模块(PLM),它提供了拟南芥莲座叶脂质代谢的机制描述。我们证明,PLM 可以很容易地集成到拟南芥 Col-0 代谢模型中,对单个致死性敲除的预测准确率达到 83%,在延长的黑暗条件下,测量的转录物和预测的通量变化之间的一致性达到 75%。通过将 PLM 集成到昼夜节律条件和特定访问模型中获得的全基因组关联与通量相关联,确定了多达 65 个候选基因,这些基因可以调节拟南芥脂质代谢。使用突变株,我们验证了多达 40%的候选基因,为基于模型识别代谢基因功能铺平了道路,这些模型可以捕捉代谢的自然变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/829cbb64431a/41467_2023_40644_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/f5cc3b4be935/41467_2023_40644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/947c34c64208/41467_2023_40644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/7afb21e18c12/41467_2023_40644_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/78756f002c73/41467_2023_40644_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/829cbb64431a/41467_2023_40644_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/f5cc3b4be935/41467_2023_40644_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/947c34c64208/41467_2023_40644_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/7afb21e18c12/41467_2023_40644_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/78756f002c73/41467_2023_40644_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bfe/10425450/829cbb64431a/41467_2023_40644_Fig5_HTML.jpg

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